Project Summary Recognition of social behavior and cell-cell signaling as a ubiquitous property of bacteria revolutionized our understanding of microbiology and microbial pathogenesis. Parasitic protozoa generally are not considered in this context. Recent work however, demonstrates that the paradigm of microbes as social organisms can and should be brought to bear on questions about parasite biology, transmission and pathogenesis. African trypanosomes, e.g. Trypanosoma brucei, and related trypanosomatid parasites are responsible for substantial human suffering worldwide. T. brucei is transmitted between human hosts by tsetse flies. The parasites live in communities in which they can communicate with one another and engage in group behaviors that are not evident in individual cells, this behavior is termed ?Social Motility? (SoMo) and shows analogies to social behavior in bacteria. Studies of SoMo provided insight into parasite signal transduction and chemotaxis, which are directly relevant for parasite development, transmission and pathogenesis. In the current proposal we will use recently discovered SoMo mutants to elucidate signal transduction mechanisms in trypanosomes and define gene expression programs that govern chemotaxis, social behavior and tsetse fly infection. We expect our studies will provide new perspectives and approaches for understanding parasite biology and for developing novel strategies for management and therapeutic intervention in parasitic disease.